Föreläsningar och seminarier CMM seminarieserie med Dominiqe Massotte
Titel: Mu-Delta Opioid Heteromers: in vivo dynamics and functional impact
Dr. Dominique Massotte, Director of Research DR2 CNRS, Institut des Neurosciences Cellulaires et Intégratives, INCI UPR3212, Strasbourg, France
Chronic administration of opiates induces tolerance and dependence, which limits their use in clinics. Mu opioid receptors mediate opiate analgesic and euphoric properties but functional crosstalk between mu and delta opioid receptors may be part of the neurobiological processes underlying opiate addiction. Heteromerization of mu-delta opioid receptors was postulated about two decade ago and signaling and trafficking properties of mu-delta heteromers have been extensively studied in transfected cells. However, little is known about their functional impact in native tissue.
Using double knock-in mice co-expressing functional fluorescent mu and delta receptors, we revealed strong mu-delta neuronal co-localization in pathways associated with nociception and opiate withdrawal and showed close physical proximity of the two receptors, which strongly supports the existence of mu-delta heteromers in the brain. We showed additional mu-delta neuronal co-expression in circuits related to drug reward, visceral control and emotional processing underlying withdrawal in morphine-dependent mice that are maintained after 4 weeks of abstinence.
Finally, we have identified modifications in mu opioid receptor trafficking and signaling resulting from mu-delta co-expression revealing functional impact of mu-delta heteromerization. These data therefore indicate that mu-delta heteromers provide additional fine-tuning of mu opioid receptor function and represent an exciting emerging concept for the development of novel therapeutic drugs and strategies.